Cradle of Cholera’s Seventh Pandemic Found

Cholera is a disease of seemingly endless fascination to epidemiologists for good reason. Vibrio cholerae emerged on a global stage in the 19th century just in time for the beginnings of modern medicine to grapple with it and for its transmission to prove the worth of epidemiological work. Although we understand its treatment and transmission well, it is still endemic in several regions, resulting in 3-5 million reported cases per year.

Like other relatively recently emerged pathogens, cholera has come in distinctive waves. Six discrete pandemics occurred between 1817 and 1923, it is believed from what is now known as the classic biotype. From 1923 to 1961 no pandemics occurred but evolution was far from standing still.  The seventh pandemic became apparent in the 1960s as the less severe El Tor biotype, that emerged sometime between 1827 and 1936, began to rapidly spread. The El Tor biotype transmits and survives better in the environment and human host than the classical biotype, including producing more asymptomatic and less severe infections.  El Tor represents an evolutionary leap forward for Vibrio cholerae on every level. We are still in the seventh pandemic. Preliminary characterization of the El Tor biotype’s mobile genetic units revealed too much diversity to reconstruct the pandemic.

Taking advantage of modern complete genome sequences, Mutreja et al (2011) collected and compared the complete genomic sequences of 136 isolates of the El Tor biotype collected over the last 40 years of the seventh pandemic plus 18 previously published genomes of El Tor and Classical biotypes. They were able to track three independent overlapping waves of cholera that are all descended from a 1950s ancestor in the Bay of Bengal. Each of these three descendant lineages left the Bay of Bengal independently for a transcontinental run.

Inferred transmission of the seventh cholera pandemic based on phylology. (Source: Mutreja et al, 2011, doi:10.1038/nature10392) Click to enlarge.

Each of the three waves can be distinguished genetically. The waves can be differentiated by the distinctive version of cholera toxin prophage carried by each clade. In addition, the first wave lacks the antibiotic cluster SXT/R391 and has obtained two VSP-2 genes. The acquisition of the SXT/R391 integrative and conjugative element (ICE) distinguishes the second wave beginning in 1978-1984. O139 strains of cholera are descended from the  second wave clone close to common ancestor of wave 1 and wave 2. The lineages within each wave have become quite complex but remain local enough not to produce waves of their own.

Each of the three waves reflects a clade of cholera that emerged from the Bay of Bengal and spread around the world, evolved into local lineages but then subsequently went extinct in non-endemic areas. Four discernible long distance transmissions have happened with the current outbreak in Haiti being the most recent. The overlapping nature and common source of these distinct waves reinforces the importance of the Bay of Bengal as cholera’s evolutionary cradle.

Considering the importance the Bay of Bengal for cholera, could other pathogens like Yersinia pestis, that has produced similar overlapping pandemic waves, also have an evolutionary cradle?  If so, then a sentinel  system set up around the cradle could give us crucial warning of an oncoming pandemic. The Bay of Bengal also serves as a lesson that knowing of the cradle is a far cry from controlling it.

Mutreja, A., Kim, D., Thomson, N., Connor, T., Lee, J., Kariuki, S., Croucher, N., Choi, S., Harris, S., Lebens, M., Niyogi, S., Kim, E., Ramamurthy, T., Chun, J., Wood, J., Clemens, J., Czerkinsky, C., Nair, G., Holmgren, J., Parkhill, J., & Dougan, G. Evidence for several waves of global transmission in the seventh cholera pandemic. (2011). Nature DOI: 10.1038/nature10392

Safa, A., Nair, G., & Kong, R. (2010). Evolution of new variants of Vibrio cholerae O1 Trends in Microbiology, 18 (1), 46-54 DOI: 10.1016/j.tim.2009.10.003

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